Some 2.8 million Americans seek medical attention for traumatic brain injury (TBI) annually, resulting in estimated annual costs of over $75 billion. Older adults have the highest and fastest rising rate of TBI of any other age-group, with 1 in 50 adults age ?75y seeking medical attention for TBI in 2013. Older adults with TBI experience higher mortality, slower recovery, worse outcomes, and may be at especially high risk for post-TBI dementia. There are few evidence-based guidelines for management, no tools to provide patients and families with reliable estimates of prognosis, and few proven treatments. Progress has been limited by: 1. systematic exclusion of older disabled patients from most prior prospective TBI studies, and 2. lack of age-appropriate TBI research tools. The overall objective is to launch a 2-site prospective geriatric TBI cohort study that will directly address these barriers by applying state-of-the-art geriatric research methods to the field of TBI to improve representation of older patients in TBI research, and to develop a novel approach to measuring age- appropriate TBI predictors, outcomes, blood-based biomarkers, and neuropathology. The approach rests on 2 foundational concepts: 1. Geriatric TBI is different from TBI in younger patients and will require a targeted age- appropriate approach. 2. Baseline health status ? including comorbidities/polypharmacy, physical frailty, functional status, and brain structure ? is recognized as a key predictor of outcome in the field of geriatrics but is not systematically measured in TBI research. The central hypothesis is that pre-injury health will be extremely heterogeneous in geriatric TBI and will be a key predictor of outcome in this population. An outstanding team of experts in TBI and aging research will achieve these Aims: Aim 1: Assemble a prospective cohort of patients age ?65y presenting to the Emergency Department ?72h after TBI who underwent CT. Enroll 270 TBI patient/study-partner dyads and 90 controls; perform baseline assessments and blood draws, and assess longitudinal outcomes at 2wk, 3mo, 6mo (primary endpoint) and 12mo; offer enrollment in a brain donation program. Aim 2: Develop and validate optimized geriatric TBI predictor and outcome assessments: 2a: Systematically measure apolipoprotein E allele and pre-injury comorbidities/polypharmacy, physical frailty, and multi-domain functional status via detailed patient and study partner interviews using validated geriatric instruments and assess association of these predictors with outcome after TBI. 2b: Describe the natural history of geriatric TBI using validated TBI and geriatric outcomes and then use data-driven analytics to identify the most parsimonious set of measures for longitudinal outcome assessment in this population. 2c (exploratory): Measure pre-injury brain structure (atrophy/white matter disease of uninjured brain visualized on baseline CT) and explore association with outcome after TBI. Aim 3: Identify age-appropriate diagnostic and prognostic blood-based biomarkers. This work will directly inform design of large-scale age-appropriate geriatric TBI clinical trials that are urgently needed to improve care and outcomes in this vulnerable population.